title: Lithium fails to enhance neurogenesis in subventricular zone and dentate subgranular zone after intracerebral hemorrhage in rats.
abstract: OBJECTIVE
  Application of lithium induces neurogenesis in the damaged brain in the global cerebral ischemia rat model. In a previous study of rats subjected to intracerebral hemorrhage (ICH), we have found that lithium treatment improves functional recovery and reduces acute brain swelling. In this follow-up study, we investigate whether the known beneficial effect of lithium on functional recovery after ICH can be explained by neurorestorative effect.
  
  
  METHODS
  Intracerebral hemorrhage was induced using infusion of collagenase into the striatum in adult rats. Rats were treated by intraperitoneal injection with lithium chloride (1, 2, or 4 mEq/kg/day) or saline for 2 weeks leading to and 2 weeks following ICH induction. From post-ICH days 4-14, 5-bromo-20-deoxyuridine (BrdU) was administered daily. At 2 weeks post-ICH, immunohistochemical staining was performed for BrdU and doublecortin (Dcx).
  
  
  RESULTS
  The neurological scores for lithium-treated rats improved significantly at 2 weeks post-ICH compared to saline-treated rats. In the subgranular zone (SGZ) and lateral subventricular zone (SVZ), numbers of BrdU-positive cells were not significantly different between the saline-treated and pooled lithium-treated groups. No significant differences in numbers of BrdU-positive cells in the SVZ were detected between the saline-treated and any of the lithium-treated groups. No significant differences in numbers of BrdU-positive cells in the SGZ were detected between the saline-treated and 1 mEq/kg lithium-treated group. Rats treated with ≧ 2 mEq/kg lithium had lower numbers of BrdU-positive cells in the SGZ than did rats treated with saline, although this difference was not statistically significant. Numbers of Dcx-positive cells in the medial striatum were not significantly different between the 1 mEq/kg lithium-treated and saline-treated groups.
  
  
  CONCLUSIONS
  The present study shows that lithium does not enhance neurogenesis after ICH in rats, and high dose lithium suppresses neurogenesis in the SGZ. Functional recovery after ICH may be attributable to neuroprotective effect, not neuroregenerative effect of lithium.
authors.forename: Kyusik
authors.initials: K
authors.lastname: Kang
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Byung-Woo
authors.initials: BW
authors.lastname: Yoon
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D018021:Lithium Chloride / Q000627:therapeutic use*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D001973:Bromodeoxyuridine; D018021:Lithium Chloride
keywords: Intracerebral hemorrhage,; Lithium,; Neural stem cell,; Neurogenesis